Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide -Drug Synthesis Database

【结构式】

【分子编号】27394

【品名】Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide

【CA登记号】100-85-6

【分子式】C₁₀H₁₇NO

【分子量】167.25112

【元素组成】C 71.81% H 10.25% N 8.37% O 9.57%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(A)

1) The cyclization of 4-cyanophenol (I) with 3-chloro-3-methylbutine (II) by means of benzyltrimethylammonium hydroxide in methanol-CH2Cl2 gives 6-cyano-2,2-dimethyl-2H-benzo[b]pyran (III), which is treated with N-bromosuccinimide in DMSO to afford 6-cyano-trans-3-bromo-3,4-dihydro-2,2-dimethyl 2H benzo[b]pyran-4-ol (IV). Epoxidation of (IV) by means of NaOH in dioxane-water yields 6-cyano-3-(4-dihydro-3,4-epoxy-2,2-dimethyl-2H-benzo[b]pyran (V), which is finally treated with 4-aminobutyric acid (VI) and NaHCO3 in refluxing ethanol. 2) By reaction of epoxide (V) with 2-pyrrolidone (X) by means of NaH in DMSO.

参考文献中间体

合成目标

【1】 Evans, J.M.; Buckingham, R.E.; Willcocks, K. (SmithKline Beecham plc); Benzopyrans. EP 0076075; JP 3014573; JP 5202034; US 4446113 .
【2】 Faruk, E.A. (SmithKline Beecham plc); Antihypertensive chromenes and chromans. EP 0093535; US 4510152 .
【3】 Castaner, J.; Mannhold, R.; BRL-34915. Drugs Fut 1986, 11, 3, 175.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	27394	Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide	100-85-6	C₁₀H₁₇NO	详情	详情
(I)	25109	4-hydroxybenzonitrile	767-00-0	C₇H₅NO	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	27395	2,2-dimethyl-2H-chromene-6-carbonitrile		C₁₂H₁₁NO	详情	详情
(IV)	27396	3-bromo-4-hydroxy-2,2-dimethyl-6-chromanecarbonitrile		C₁₂H₁₂BrNO₂	详情	详情
(V)	12861	2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile		C₁₂H₁₁NO₂	详情	详情
(VI)	13620	4-Amino-n-butyric acid; 4-Aminobutyric acid;Piperidinic acid;Piperidic acid	56-12-2	C₄H₉NO₂	详情	详情
(X)	27397	2-Pyrrolidinone	616-45-5	C₄H₇NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(A)

The reaction of epoxide (V) with ammonia in ethanol gives 4-amino-6-cyano-3,4-dihydro-2,2-dimethyl-trans-2H-benzo[b]pyran-3-ol (VII), which is condensed with 4-chlorobutyryl chloride (VIII) by means of NaOH in CHCl3 yielding 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(4-chlorobutyrylamino)-2H-benzo[blpyran 3-ol (IX). Finally, this compound is cyclized by means of NaH in THF.

参考文献中间体

合成目标

【1】 Faruk, E.A. (SmithKline Beecham plc); Antihypertensive chromenes and chromans. EP 0093535; US 4510152 .
【2】 Evans, J.M.; Buckingham, R.E.; Willcocks, K. (SmithKline Beecham plc); Benzopyrans. EP 0076075; JP 3014573; JP 5202034; US 4446113 .
【3】 Castaner, J.; Mannhold, R.; BRL-34915. Drugs Fut 1986, 11, 3, 175.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	27394	Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide	100-85-6	C₁₀H₁₇NO	详情	详情
(I)	25109	4-hydroxybenzonitrile	767-00-0	C₇H₅NO	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	27395	2,2-dimethyl-2H-chromene-6-carbonitrile		C₁₂H₁₁NO	详情	详情
(IV)	27396	3-bromo-4-hydroxy-2,2-dimethyl-6-chromanecarbonitrile		C₁₂H₁₂BrNO₂	详情	详情
(V)	12861	2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile		C₁₂H₁₁NO₂	详情	详情
(VII)	27398	(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromene-6-carbonitrile		C₁₂H₁₄N₂O₂	详情	详情
(VIII)	11265	4-Chlorobutanoyl chloride; 4-Chlorobutyric acid chloride	4635-59-0	C₄H₆Cl₂O	详情	详情
(IX)	27399	4-chloro-N-[(3S,4R)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]butanamide		C₁₆H₁₉ClN₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The condensation of fluorene-9-carboxamide (IV) with acrylonitrile (V) by means of benzyltrimethylammonium hydroxide (VI) in hot dioxane gives 9-carbamoyl-9-(2-cyanoethyl)fluorene (VII), which is then hydrogenated and condensed with isopropylamine (VIII) and H2 over PtO2 with the same isopropylamine (VIII) as solvent.

参考文献中间体

合成目标

【1】 Lavagnino, E.R.; Pike, A.J.; Campbell, J.B. (Eli Lilly and Company); 9-Carbamoyl-9-(2-cyanoethyl)fluorenes. DD 158395; EP 0038676; GB 2074161; JP 1125363; US 4282170 .
【2】 Serradell, M.N.; Sneddon, J.; Castaner, J.; Indecainide. Drugs Fut 1985, 10, 2, 121.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	28969	9H-fluorene-9-carboxamide		C₁₄H₁₁NO	详情	详情
(V)	28970	3-butenenitrile	109-75-1	C₄H₅N	详情	详情
(VI)	27394	Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide	100-85-6	C₁₀H₁₇NO	详情	详情
(VII)	28971	9-(2-cyanoethyl)-9H-fluorene-9-carboxamide		C₁₇H₁₄N₂O	详情	详情
(VIII)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

合成路线4

该中间体在本合成路线中的序号：(B)

7-Chloro-3-hydroxy-5-(2'-fluorophenyl)-1,3-(dihydro-2H-1,4-benzodiazepin-2-one (I) is mixed with acrylonitrile (II), and after dropwise addition of triethylbenzylammonium chloride (A) and benzyl trimethylammonium hydroxide (B), stirring is continued for 8 hours. The crude material was recrystallized from acetonitrile.

参考文献中间体

合成目标

【1】 Schlager, L.H. (Gerot Pharmazeutika GmbH); Novel 3-hydroxy-1,4-benzodiazepine-2-ones and process for the preparation thereof. AT 361492B; DE 2950235; ES 8103738; FR 2444672; US 4388313 .
【2】 Koch, H.; Cinolazepam. Drugs Fut 1982, 7, 2, 98.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	27394	Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide	100-85-6	C₁₀H₁₇NO	详情	详情
(A)	31937	Triethylbenzylammonium chloride; N-benzyl-N,N-diethyl-1-ethanaminium chloride; Benzyltriethylammonium chloride	56-37-1	C₁₃H₂₂ClN	详情	详情
(I)	31936	7-chloro-5-(2-fluorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₁₅H₁₀ClFN₂O₂	详情	详情
(II)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情

Extended Information